During the past year we have continued investigations utilizing a model in which a 30% liver transplant (from a donor ssubjected to 70% PH) is connected in tandem with an intact host liver. That liver demonstrates DNA synthesis following transplantation. It has been demonstrated that following the creation of an isolated ileal loop such synthesis is significantly decreased. Additional investigations have been carried out to further evaluate the role of the intestine in the regenerative process. Since in prior studies DNA synthesis was determined only 24 hours following PH and ileal loop isolation, the possibility was considered that there may only been a delay in DNA synthesis. Studies recently carried out indicate that up to at least 3 days there is no delayed increase in DNA synthesis. Other studies have evaluated the technic of vascular ligation employed in intestional resection on DNA synthesis, the effect of removal of a segment of large intestine of liver regeneration, and the effect of perfusion of an isolated segment of intestine with saline on DNA synthesis following PH. In the latter studies, such perfusion was found to ameliorate the depression of DNA synthesis. More recently our investigations have been directed toward evaluating mechanisms involved in the restoration of liver macrophages following PH. Evidence by others suggests that cells repopulate the liver from the circulation and are not replicated by those remaining. Measuring macrophage colony production by culture of bone marrow cells in semi-solid medium we have observed an increase in their production following PH providing the first such information. The administration of Corynebacterium parvum, an immunostiumlating agent has been found by us to markedly increase liver weight, DNA synthesis and total liver DNA. Consequently, the effect of that agent in PH aminals (before/after PH) will be evaluated. In addition, its effect on the atrophy of portacaval shunt will be investigated.